1. Quality of life and its health- relations

2. Definitions

3. Subjective Multi-dimensional Dynamic Physical Functioning Social Functioning Emotional Functioning

4. Outcome Assessment Disease level (lab data) (clinical data) Patient level (lab data) (clinical data)

5. Why assess health-related quality of life in cancer patients Consumerism and outcome research drive Helps design new approaches/monitor effectiveness Improve clinicians’ knowledge of patients’ subjective experience Health economic evaluation Reliable HRQOL outcome can help give a comprehensive picture of the treatment outcome supporting decision-making policy

6. Who can best assess QOL Doctor and nurses consistently underestimate patients’ levels of QOL Patients are the best judge of their subjective well-being BUT Difficult scientific methodology Requires good doctor-patient communication Requires collaboration with other experts Resource intensive (assistants, nurses)

7. How should we assess QOL EORTC QLQ-C30 Questionnaire FACT-G – Functional Assessment of Cancer Therapy FLIC – Functional Living Index for Cancer Rotterdam Symptom Checklist

8. EORTC-QLQ C30

9. Minimum important difference (MID) The smallest difference in score in the outcome of interest Which patients perceive as beneficial And which would mandate, in the absence of troublesome side effects and excessive cost, a change in the patient’s management

10. MID 10 point difference on a 0-100 scale, EORTC’s QLQ suite, widely used as threshold for clinically important different

11. MID ComparisonImprovedDeteriorated Ringash et al.Other patients4.48.3 Cella et al., 2002 Own rating of change over time 5.59.9 Cella et al., 1997 Change in Karnofsky PS 5.46.8

12. Measuring Quality of Life in Routine Oncology Practice Improves Communication and Patient Well-Being Velikova et al. J Clin Oncol 2004; 22: 714-724. The intervention 1.QOL evaluated by EORTC QLQ-C30 before seeing the doctor 2.QOL graphs attached to medical notes; Physicians review QOL results 3.After each intervention the physicians filled visit-specific checklist 4.Patients imopression on communucation was recorded

13. Discussion Regular QOL measurements has positive impact on: – Physician-patient communication – Patient well-being Symptom control and emotional well-being – Improvement in patient well-being was associated with explicit use of QOL information during consultations

14. Opinions Participating patient: – I felt that people were still interested in me. People were still wanting to know. I wasn’t written off altogether. Participating physician: – I actually think that’s the most powerful thing.

15. Baseline quality of life as prognostic indicator of survival: a meta-analysis of individual patient data from EORTC clinical trials. Quinten C et al. Lancet Oncology, 2009; 10: 865-71. Trial Data: 30 EORTC Trials 11 cancer sites 10.108 patients Pre-intervanetion QOL measures

16. Results Final Model HRMA Estimate HR Inclusion variable (%) WHO=0-1 vs. WHO=2-3 1.07 100 Age 601.17 100 Non-meta vs. Meta1.70 100 Male vs. Female0.74 100 Physical functioning0.940.95100 Pain1.04 99.7 Appentite Loss1.05 100

17. Conclusion QOL parameters: pain, physical functioning, appetite loss provide prognostic information beyond clinical measures. This effect holds across the different diseases sites and therefore taking into account QOL parameters can improve survival prediction of cancer patients

18. Genetics and QOL The heritability of self-reported health 4.638 male-male twins Regression model Genetic variables accounted for 33% of the variability in self-reported health

19. QOLenomics? The study of how inherited genetic variations affect aspects of patient quality of life as well as the use of that knowledge in treatment discovery and development Could genetic variation explain why one person experiences profound deficits in QOL while another person reports no QOL deficits from the same disease?

20. Preliminary Evidence of Relationship Between Genetic Markers and Oncology Patient QOL Prior to Treatment JA Sloan et al. Mayo Clinic Camprehensive Cancer Center Background – Genetic predispositions exist for depression, suicide, alcoholism, smoking and other psychological variables 5-HT receptor APOE epsilon 4 allele Androgen-regulator genes

21. Study plan 22 candidate genes variants in 11 genes ebaluated 494 patients with both genetic samples and QOL data at baseline

22. Results DPYD*5 was significantly associated with patient-reported fatigue (p=0.008) The homozygous variant was associated with lower fatigue scores (worse QOL)

23. DPYD DPYD gene: – Involved in pyrimidine base degradation – Catalyzes the reduction of uracil and thymine – Only endogenous source of neurotransmitter B- alanine DPYD*5/*6 polymorphism: – Could be in linkage disequilibrium with another genetic variant that directly affects cellular metabolism, and thus QOL.

24. Implications Identify cancer patients with genetic predisposition for deficits in QOL Effective pharmacologic and psychosocial interventions exist for QOL Genetically-targeted, individualized treatments for QOL might be possible